Cutaneous nodules and a novel GNAS mutation in a Chinese boy with pseudohypoparathyroidism type Ia: A case report and review of literature

BACKGROUND Pseudohypoparathyroidism type Ia(PHP Ia) is a rare hereditary syndrome, and patients with early PHP Ia are generally not diagnosed based on the presentation of cutaneous nodules as the main clinical feature. Here, we describe a Chinese boy with PHP Ia in whom the main clinical feature was cutaneous nodules, and the patient exhibited a novel GNAS mutation.CASE SUMMARY A 5-year-old boy presented with a 5-year history of cutaneous nodules scattered over his entire body. The patient had a short stature, round face, short neck, and slightly flattened nose;he also had multiple hard papules and cutaneous nodules scattered over his entire body. The patient had a significantly elevated parathyroid hormone level. His serum calcium level was reduced, while his serum phosphorus level was increased and his serum thyroid-stimulating hormone level was elevated. Skin biopsy showed osteoma cutis in subcutaneous tissue. Sanger sequencing revealed a frameshift mutation, c.399 del T(p.Ser133 Argfs*2) in exon 5 of the GNAS gene. The patient was diagnosed with PHP Ia and subclinical hypothyroidism. He was given 1,25-dihydroxyvitamin D,calcium carbonate, and synthetic L-thyroxine. After 3 months of treatment, the patient’s parathyroid hormone level decreased, and his serum calcium and serum phosphorus levels were normal. Moreover, his thyroid-stimulating hormone level decreased.CONCLUSION These findings can help dermatologists to diagnose PHP Ia in patients with cutaneous nodules as the main early clinical feature.

Fahr’s Syndrome Discovered at Adulthood Revealing the Pseudohypoparathyroidism

Fahr’s syndrome is a rare clinicopathological entity, defined by the presence of intracerebral calcifications not arteriosclerotic, bilateral and symmetric at the level of the basal ganglia, whose main etiology is dysparathyroidism, rarely pseudohypoparathyroidism. Hypocalcemia and hyperphosphatemia despite normal or high levels of parathyroid hormone are the result of resistance to the action of parathyroid hormone. The clinical profile is not specific but dominated by neuropsychiatric symptoms. We report the case of a 30-year-old patient with type pseudohypoparathyroidism revealed one year ago by Fahr’s syndrom. The diagnosis made by convulsion history since the age of 5 years resistant to treatment, the disturbance of metabolism disorders, and the presence of intracerebral calcifications. The vitamin D and calcium supplementation have contributed to the stabilization of the disease.

Treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism with domestic-made calcitrioh a prospective and self-controlled clinical trial

Background Parathyroid hormone deficiency or resistance may cause hypocalcemia with related symptoms and signs. Lifelong treatment of calcium combined with vitamin D or its metabolites is always necessary for these patients. Here we reported a prospective and open-label trial to investigate the efficacy and safety of domestic-made calcitriol in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism. Methods Twenty-four patients with confirmed hypoparathyroidism or pseudohypoparathyroidism aged （36.5±11.0） years old were studied. Among them, 16 patients had idiopathic hypoparathyroidism, 2 had pseudohypoparathyroidism and 6 had hypoparathyroidism secondary to cervical surgery. Serum calcium levels were lower than 1.88 mmol/L. Oral calcitriol was administered twice or three times with elemental calcium 1.2 g per day. All patients were followed every 4 weeks throughout the 12-week period. Dose adjustments of calcitriol were based on serum and urinary calcium levels and symptoms of hypocalcemia. Results Twenty patients were included by the end of this study. Muscular weakness, cramps, extremity paresthesia, Chovestek＇s sign and Trousseau＇s sign were relieved in 76.9%, 100%, 94.4%, 93.3% and 78.9% of patients, respectively. Serum calcium, plasma ionized calcium and serum phosphorus levels were （1.54±0.25） mmol/L, （0.64±0.10） mmol/L and （2.00±0,46） mmol/L at baseline, and reached （2.20±0.20） mmol/L, （0.95±0.06） mmol/L and （1.68±0.25） mmol/L （P 〈0.01） at the 12th week of treatment, respectively. Eighty percent of patients were assessed as effective and 20% as partly effective. Three, four and eight patients had hypercalciuria at the 4th, 8th and 12th week of treatment, respectively, which were reduced by thiazide diuretics. The final dose of calcitriol was （1.09±0.50） ug/d. Conclusions Calcitriol combined with calcium can be used in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism effectively and safely. Serum and urinary calcium levels should be monitored during the course of the therapy.

Neuropsychic Disorders Unmasking the Coexistence of Fahr Syndrome and Neuromeningeal Cryptococcosis

Background: Fahr syndrome associates a set of neuropsychiatric manifestations with bilateral calcifications in the basal ganglia and phosphocalcic disorders. Neuromeningeal cryptococcosis can be present in its manifestations, neuropsychic disorders with or without meningeal signs. The objective was to describe a rare association between Fahr syndrome and neuromeningeal cryptococcosis which can be expressed by the same clinical symptomatology in the context of co-infection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV). Presentation: A 37-year-old patient without pathological history, who presented behavioral disorders that led to a fight with those around her and a psychiatric consultation. Then, she was hospitalized in the infectious diseases Department upon discovery of her HIV status and viral hepatitis B. She was logorrheic with behavioral disturbances and subsequently presented with tonic-clonic convulsions. Laboratory tests and imaging have concomitantly discovered Fahr syndrome due to pseudohypoparathyroidism and neuromeningeal cryptococcosis. The correct management of these two pathologies enabled stabilization of the patient’s clinical condition with regular monitoring for HIV-HBV coinfection. Conclusion: Farh syndrome and neuromeningeal cryptococcosis are two different entities but sometimes similar symptoms and risk factors. Treatment of metabolic disorders combined with anticryptococcal therapy improved the prognosis.