Pseudohypoparathyroidism Type 1A-Subclinical Hypothyroidism and Rapid Weight Gain as Early Clinical Signs: A Clinical Review of 10 Cases

OBJECTIVE: To evaluate the clinical signs and symptoms that would help clinicians to consider pseudohypoparathyroidism (PHP) type 1A as a diagnosis in a child. METHODS: A retrospective review of the medical records of children diagnosed by erythrocyte Gsα activity and/or GNAS1 gene study and followed-up for PHP type 1A. Clinical and biochemical parameters along with epidemiological data were extracted and analyzed. Weight gain during infancy and early childhood was calculated as change in weight standard deviation score (SDS), using the French growth reference values. An upward gain in weight ≥0.67 SDS during these periods was considered indicative of overweight and/or obesity. RESULTS: Ten cases of PHP type 1A were identified (mean age 41.1 months, range from 4 to 156 months). In children aged ≤2 years, the commonest clinical features were round lunar face, obesity (70%), and subcutaneous ossifications (60%). In older children, brachydactyly was present in 60% of cases. Seizures occurred in older children (3 cases). Short stature was common at all ages. Subclinical hypothyroidism was present in 70%, increased parathormone (PTH) in 83%, and hyperphosphatemia in 50%. Only one case presented with hypocalcemia. Erythrocyte Gsα activity tested in seven children was reduced; GNAS1 gene testing was performed in 9 children. Maternal transmission was the most common (six patients). In three other cases, the mutations were de novo, c.585delGACT in exon 8 (case 2) and c.344C>TP115L in exon 5 (cases 6&7). CONCLUSION: Based on our results, PHP type 1A should be considered in toddlers presenting with round face, rapid weight gain, subcutaneous ossifications, and subclinical hypothyroidism. In older children, moderate mental retardation, brachydactyly, afebrile seizures, short stature, and thyroid-stimulating hormone resistance are the most suggestive features.