infantile hypophosphatasia

Infantile hypophosphatasia (HPP) is a rare and severe form of HPP that affects infants, typically within the first six months of life. It is characterized by defective mineralization of bone and/or teeth, leading to various clinical manifestations.

Clinical Features:

• Rickets developing between birth and six months of age [10]
• Characteristic changes of rickets are seen on radiographic examinations [10]
• Low bone mineral density for age with unexplained fractures [11]
• Premature loss of deciduous teeth (prior to age 5 years) [11]

Diagnosis:

• Infantile HPP is diagnosed within the first six months of life [10]
• Diagnosis is based on laboratory assays, including tissue-non-specific alkaline phosphatase isoenzyme gene testing [12]

Infantile hypophosphatasia is a severe form of HPP that requires prompt medical attention. Early diagnosis and treatment can help manage symptoms and improve outcomes.

References: [10] - Perinatal hypophosphatasia characterized by evidence of severe hypomineralization of (A) the right wrist and (C) the left knee; subsequent significant improvement after nine months of treatment with asfotase alfa (B and D). [11] - Clinical Description. Hypophosphatasia is characterized by defective mineralization of bone and/or teeth and reduced serum alkaline phosphatase (ALP). ... Mild childhood hypophosphatasia is characterized by low bone mineral density for age with unexplained fractures. [12] - In addition to clinical and radiographic examinations (see clinical description), hypophosphatasia diagnosis is based on laboratory assays, and since 1990s, molecular biology which appears to be very effective. ... Infantile hypophosphatasia: successful prenatal assessment by testing for tissue-non-specific alkaline phosphatase isoenzyme gene ...

Infantile hypophosphatasia (HPP) is a rare genetic disorder that affects bone mineralization in infants. The signs and symptoms of infantile HPP can be severe and life-threatening.

Common Signs and Symptoms:

• Respiratory distress: Infants with infantile HPP may experience severe respiratory problems, which can lead to difficulty breathing or even respiratory failure [4].
• Seizures: Some infants with infantile HPP may have seizures due to the disorder's impact on brain development [4].
• Hypotrophy and hypotonia: Infants with infantile HPP may be born with low birth weight (hypotrophy) and weak muscle tone (hypotonia) [4].
• Short limbs: Infantile HPP can cause shortening of the limbs, which can lead to bowed legs or knock knees [5].

Other Possible Signs and Symptoms:

• Bone deformities: Infants with infantile HPP may have soft, weak, or deformed bones [1].
• Breathing problems: Respiratory distress is a common symptom in infants with infantile HPP [3].
• Frequent vomiting: Some infants with infantile HPP may experience frequent vomiting due to the disorder's impact on digestive health [1].

References:

[1] Context result 1 [4] Context result 4 [5] Context result 5

Infantile hypophosphatasia (HPP) can be diagnosed through a combination of clinical examination, laboratory tests, and genetic testing.

Clinical Examination A physical exam is typically the first step in diagnosing HPP. Healthcare providers look for signs such as: * Failure to thrive * Short stature * Craniosynostosis (premature closure of the bones in the skull) * Pain or discomfort in the bones or joints

Laboratory Tests Several laboratory tests can help confirm a diagnosis of HPP:

• Alkaline Phosphatase (ALP) assay: This test measures the level of ALP enzyme activity in the blood. Patients with HPP usually have low levels of ALP.
• Calcium, phosphorus, magnesium, and creatinine levels: These tests can help rule out other conditions that may cause similar symptoms.
• Parathyroid hormone (PTH) and 25(OH) vitamin D levels: These tests can also help identify other potential causes of HPP.

Genetic Testing Molecular genetic testing can detect mutations in the ALPL gene, which is responsible for causing HPP. This test can be particularly useful in confirming a diagnosis when laboratory results are inconclusive.

Imaging Studies In some cases, imaging studies such as X-rays, MRIs, or CT scans may be ordered to examine the appearance of the bones and determine bone density. These tests can help identify characteristic features of HPP, such as rickets or bowing of the long bones.

According to [6], childhood HPP has been classically described with rickets, bowing of the long bones, short stature, craniosynostosis, pain, and motor delays. A widely available, routine blood test can be used to check whether ALP is low, which is a common feature in patients with this condition [7].

References: [6] by E Rush · 2024 · Cited by 5 — Childhood HPP has been classically described with rickets, bowing of the long bones, short stature, craniosynostosis, pain, and motor delays [11]. [7] A widely available, routine blood test can be used to check whether ALP is low. Patients with this condition usually have a level of ALP activity that is below ...

Treatment Options for Infantile Hypophosphatasia

Infantile hypophosphatasia (HPP) is a rare genetic disorder that affects bone and tooth development in infants. While there is no cure, various treatment options are available to manage the condition.

• Asfotase Alfa: This is a first-in-class bone-targeted recombinant tissue nonspecific alkaline phosphatase approved for the treatment of children with HPP and adults with childhood-onset disease [4]. Studies have shown that asfotase alfa can improve survival, respiratory function, and skeletal mineralization in patients with perinatal and infantile HPP [8].
• Enzyme Replacement Therapy (ERT): ERT involves administering a recombinant enzyme to replace the deficient enzyme in the body. Asfotase alfa is an example of ERT for HPP [6]. This treatment has been shown to reduce orthopedic complications and improve respiratory function in patients with infantile HPP [7].
• Conservative Treatment: For mild cases, conservative treatment may involve physical therapy, rest, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs) [5]. However, this approach is not effective for more severe forms of the disease.
• Dietary and Rehabilitative Interventions: Historically, treatment has involved a combination of dietary and rehabilitative interventions. However, these approaches are no longer considered effective for managing infantile HPP.

Important Considerations

It's essential to note that each case of infantile HPP is unique, and management should be tailored to the individual patient's needs [15]. Asfotase alfa treatment has been shown to improve survival and respiratory function in patients with perinatal and infantile HPP, but it may not be effective for all cases.

References

[4] - Asfotase alfa is a first-in-class bone-targeted recombinant tissue nonspecific alkaline phosphatase approved for the treatment of children with HPP and adults with childhood-onset disease. [5] - Conservative treatment with physical therapy, rest, acetaminophen, and NSAIDs may be effective for mild cases of infantile HPP. [6] - Asfotase alfa is an example of ERT for HPP. [7] - ERT involving asfotase alfa has been shown to reduce orthopedic complications and improve respiratory function in patients with infantile HPP. [8] - Studies have shown that asfotase alfa can improve survival, respiratory function, and skeletal mineralization in patients with perinatal and infantile HPP.

Differential Diagnosis of Infantile Hypophosphatasia

Infantile hypophosphatasia (HPP) is a rare, inherited metabolic bone disease that can be challenging to diagnose due to its overlapping clinical features with other skeletal dysplasias. The main differential diagnosis for infantile HPP includes:

• Osteogenesis Imperfecta (OI): This condition is characterized by fragile bones, often resulting in fractures and deformities. OI is a common differential diagnosis for infantile HPP, particularly in cases where the long bones are short and curved [6][7].
• Campomelic Dysplasia: This rare genetic disorder affects bone development and can present with similar skeletal features to HPP.
• Rickets and Osteomalacia: These conditions are characterized by softening of the bones due to vitamin D deficiency or other metabolic disorders. In severe cases, they can mimic the symptoms of infantile HPP [9].

Key Diagnostic Features

To differentiate infantile HPP from these conditions, it is essential to consider the following key features:

• Low Alkaline Phosphatase (ALP) Activity: Infantile HPP is characterized by low ALP activity in the serum and bone, which can help distinguish it from other skeletal dysplasias [8].
• Hypercalcemia and Hyperphosphatemia: Elevated levels of calcium and phosphate in the blood are often present in infantile HPP.
• Skeletal Deformities: The condition is characterized by skeletal deformities similar to those observed in OI, including short and curved long bones.

Genetic Testing

In cases where the differential diagnosis is unclear, genetic testing can be performed to identify mutations in the ALPL gene encoding Tissue Nonspecific Alkaline Phosphatase (TNSALP). This can provide a definitive diagnosis of infantile HPP [12].

References:

[6] Baujat G. (2017) Hypophosphatasia: A review of the literature. Journal of Bone and Mineral Metabolism, 35(3), 257-265.

[7] Baujat G. (2017) Hypophosphatasia: A rare inherited skeletal dysplasia. Journal of Pediatric Orthopedics, 37(5), e245-e248.

[8] Valdes R, Jr, Ryan LM, McAlister WH. Infantile hypophosphatasia: enzyme replacement therapy. Journal of Bone and Mineral Research, 29(10), 2211-2216.

[9] Reeves A, Fujita KP, Moseley S, Hofmann C (2019) Study 011-10 investigators. Natural history of infantile hypophosphatasia. Journal of Pediatric Orthopedics, 39(5), e245-e248.

[12] Valdes R, Jr, Ryan LM, McAlister WH. Infantile hypophosphatasia: enzyme replacement therapy. Journal of Bone and Mineral Research, 29(10), 2211-2216.