Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies

Table 3 Symptoms and signs described in the different BH₄ deficiencies

	PTPSD	DHPRD	AR-GTPCHD	SRD	PCDD	AD-GTPCHD
Number of reported cases	125	77	55	53	19	570
Nervous system
Developmental delay	+++	+++	+++	+++	+	(+)
(Axial) Hypotonia	+++	++	+++	+++	+	(+)
Poor head control	+	+	+	+		(+)
Hypertonia	++	++	++	++	(+)	++
Epilepsy	++	+++	+	+
Cognitive impairment	++	+	(+)	++		(+)
Impaired speech development	+	(+)	(+)	+++		(+)
Dysarthria	(+)	(+)		+++		(+)
Movement disorders
Diurnal fluctuation of symptoms			+	+++		+++
Dystonia	+	+	++	+++		+++
Oculogyric crises	(+)	+	(+)	+++		(+)
Gait difficulties						+++
Dyskinesia/other involuntary movements	+	+	(+)	+/++
Parkinsonism/hypokinesia	+	(+)/+	+	+++		+
Tremor	(+)	(+)	(+)		(+)	+
Ataxia	(+)	(+)		+		(+)
Other
Hyperreflexia	(+)/+	+				++
Irritability	(+)/+	+
Microcephaly		++	(+)	(+)
Autonomous nervous system
Temperature instability	(+)	(+)	++	++
Gastrointestinal system
Hypersalivation	(+)	+	++	+/++
Feeding/swallowing difficulties	+	+	(+)	++		(+)
Psychological problems
Behavioural problems	(+)	(+)		(+)
Psychiatric problems	(+)	(+)		++		+
Sleep problems	(+)	(+)		++		(+)
Endocrine disturbances
Growth-hormone deficiency	(+)
Low birth weight	++
Central hypothyroidism				(+)
MODY3-like diabetes					+
Other
Microcephaly		++	(+)	(+)
Fatigability	(+)	+		(+)		(+)
Recurrent chest infections	+
Prematurity	+	+
Hypomagnesemia					+

Symptoms and signs reported in 570 Patients with AD-GTPCHD, 55 patients with AR-GTPCHD, 125 patients with PTPSD, 77 patients with DHPRD, 53 patients with SRD and 19 patients with PCDD
Very frequently +++ (≥50%), frequently ++ (≥25- < 50%), infrequently + (≥10- < 25%), occasionally (+) (< 10%)

ISSN: 1750-1172