Neuropsychiatric phenotype in a child with pseudohypoparathyroidism

Abstract

Pseudohypoparathyroidism (PHP) is a rare heterogeneous genetic disease characterized by end-organ resistance to parathyroid hormone. In adulthood, heterogeneous neurological and psychiatric disorders have been reported which are associated with hypoparathyroidism in general and with PHP in particular, while for childhood, data are scanty. We report a case of a boy with PHP type 1b, in whom neurological signs at the onset prevailed, characterized by tic-like dyskinesias associated with a series of heterogeneous not well-defined neurological and behavioral features, describing the diagnostic work-up performed and the follow-up. We suggest that the diagnostic hypothesis of PHP might be considered when dealing with a child with tic-like dyskinesias, especially if associated with a series of heterogeneous not well-defined neurological and behavioral features. In these cases, treatment with calcitriol and calcium has to be started as soon as possible to achieve a prompt and persistent clinical improvement.

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

“…Patients with PHP1A present with psychomotor and cognitive abnormalities, which are defined as a history of developmental delay and learning disability, with reduced performance on the Wechsler intelligence scale 24,42,262 and an increased incidence of psychiatric manifestations that might be the consequence of the disease or of long-term hypocalcaemia 42,207 .…”

“…Intellectual disability seems to be more prevalent in patients with PHP1A than in patients with PPHP, which suggests that G s α is imprinted in the brain 24,214,229 . The existence of neurological manifestations or true neuropsychiatric phenotype due to organic CNS alterations, and specifically Chiari malformation type 1, should be considered 38,207,265 . Finally, the prevalence and severity of cognitive impairment and developmental delay vary among patients with acrodysostosis, but a detailed clinical description is lacking 5,6,14,63,266 .…”

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients

“…One retrospective review of developmental milestones showed a greater delay in language compared with gross motor skills, with and a tendency to improve during late childhood [6]. Neurological and neuropsychiatric manifestations can be linked to the function in addition to the role of Gsα in brain development [84], and other organic CNS alterations, including Chiari 1 malformation [85-87] or prolonged periods of hypocalcemia [83, 87] found in some patients. Patients with PHP and related disorders should be referred to a neuropsychologist for neurocognitive and/or behavioral assessment at diagnosis or at preschool age, especially patients with PHP1A and acrodysostosis due to PDE4D pathogenic variants mutations.…”

Fahr´s Syndrome; Pseudohypoparathyroidism Type Ib Masquerading as Epileptic Seizures

“…Hypocalcaemia due to vitamin D deficiency, hypoparathyroidism or PHP can lead to manifest tetany, presenting as epileptic seizures, together with muscle cramps and pain, severe muscle weakness, and psychomotor retardation. [1][2][3][4][5][6][7][8][9] Our patient was initially considered as suffering from epilepsy, however the abnormal values of calcaemia and phosphataemia pointed to another etiology of the convulsions and his neuromuscular and neuropsychic problems. The massive intracerebral calcifications were initially suggestive of Fahr´s disease, which is a rare heritable or sporadic neurodegenerative disorder characterized by basal ganglia calcification, and presenting with diverse neuropsychiatric manifestations.…”

“…[1][2][3][4][5][6] These symptoms can be initially considered as signs of epilepsy. [4][5][6][7][8][9] In known epilepsy, hypocalcaemia lowers the threshold for seizure activity. [1][2][3][4] We present a paediatric patient, initially diagnosed as having epilepsy, where severe hypocalcaemia, due to pseudohypoparathyroidism (PHP) was the underlying cause.…”